A chemical biology screen identifies a vulnerability of neuroendocrine cancer cells to SQLE inhibition.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30626880.
- Also identified by DOI 10.1038/s41467-018-07959-4 and PMC identifier 6327044.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Aberrant metabolism of cancer cells is well appreciated, but the identification of cancer subsets with specific metabolic vulnerabilities remains challenging. We conducted a chemical biology screen and identified a subset of neuroendocrine tumors displaying a striking pattern of sensitivity to inhibition of the cholesterol biosynthetic pathway enzyme squalene epoxidase (SQLE). Using a variety of orthogonal approaches, we demonstrate that sensitivity to SQLE inhibition results not from cholesterol biosynthesis pathway inhibition, but rather surprisingly from the specific and toxic accumulation of the SQLE substrate, squalene. These findings highlight SQLE as a potential therapeutic target in a subset of neuroendocrine tumors, particularly small cell lung cancers.
Medical subject headings
- Antineoplastic Agents
- Drug Delivery Systems
- Drug Screening Assays, Antitumor
- Squalene Monooxygenase